In postnatal rat tissues, ovine placental lactogen (oPL) and ovine growth hormone (oGH) have similar biologic actions, and the effects of both hormones are thought to be mediated through binding to "growth hormone receptors". However, in fetal rat tissues, oPL has somatotropic and metabolic effects but oGH has little or no biologic activity. The overall objectives of this research proposal are to examine the biologic effects of oPL and oGH in tissues of the ovine fetus and to investigate the cellular basis for the marked differences in the metabolic effects of oPL and oGH in the fetus. Firstly, the effects of oPL and oGH on glycogen metabolism in cultured hepatocytes from fetal sheep will be examined. These studies should determine whether the potency of oPL in the fetal sheep, as in the fetal rat, greatly exceeds that of oGH. Secondly, the ontogeny and structures of placental lactogen and growth hormone receptors will be examined. The total specific binding and relative binding potencies of oPL and oGH to ovine hepatic membranes will be determined in livers of fetal sheep at 70, 110 and 140 days of gestation and from postnatal sheep three months after birth. Dose-response curves for the binding of labelled hormones in the presence of varying concentrations of unlabelled hormones will be determined. Scatchard analysis of the binding data will be employed to assess ontogenetic changes in total receptor concentration, receptor affinity, and possible receptor cooperativity. The structures of the membrane binding sites for oPL and oGH in fetal and postnatal sheep liver will be examined by polyacrylamide gel electrophoresis of covalently coupled hormone-receptor complexes in the presence or absence of dithiothreitol. Radioactively-labelled hormones will be coupled to their respective membrane binding proteins with disuccinimidyl suberate, a bifunctional cross-linking agent, and gels will be analyzed by autoradiography. Analysis of the results should determine whether oPL binds to specific placental lactogen receptors in the fetus which differ in structure and/or function from the growth hormone receptors in postnatal tissues. The results of receptor binding studies will be related to the effects of oPL and oGH on glycogen metabolism in cultured hepatocytes from fetal sheep. The findings should provide information about the cellular mechanisms by which placental lactogen and growth hormone regulate fetal and postnatal growth.